Dideoxypyrimidine and purine nucleosides have been synthesized as agents to protect ATH8 cells from the cytopathic effect of the virus which causes AIDS (HIV). 5-Fluoro-2', 3'-dideoxycytidine (5- F-ddC) is as potent and protective as the parent drug, dideoxycytidine (ddC). The fluoro compound is 30 times less basic than the ddC and appears to have about three times the oral bioavailability of ddC in the mouse. All other comparisons show essentially identical properties. Toxicity studies will be designed to determine if 5-F-ddC has an advantage over ddC. 5-F-ddC also should be a useful PET scan drug for studying the pharmacology of ddC. Several other pyrimidine dideoxynucleosides have been prepared for anti-AIDS testing and pharmacological evaluation. Dideoxyadenosine (ddA) is an anti-AIDS drug scheduled for clinical trial during FY 87. It is very unstable under acidic conditions, making an oral formulation of the drug difficult. 2', 3'-dideoxy-2'-beta-fluoroadenosine (2'-F-ddA) has been synthesized and found to be just as active and potent as ddA in HIV tests. In addition, 2'-F-ddA undergoes no decomposition after 24 hours under the acidic conditions which give ddA a half-life of 35 seconds.